Aphasia Patients’ Responses to Brain Stimulation May Predict their Extent of Language Recovery – Phase I

Roy Hamilton, M.D.

University of Pennsylvania, Philadelphia, PA

Grant Program:

David Mahoney Neuroimaging Program

Funded in:

April 2014, for 3 years

Funding Amount:


Lay Summary

Aphasia patients' responses to brain stimulation may predict their extent of language recovery - Phase I

Researchers will undertake Phase I of a planned two-phase study to determine whether responses by aphasic stroke patients to a form of non-invasive brain stimulation, called transcranial magnetic stimulation, predict their capacity for brain plasticity and recovery of language function.

Aphasia results from damage to the brain’s language areas and can impair language expression, understanding, and speech. About a third of the estimated 800,000 people annually who suffer a stroke in this country develop aphasia. The extent of language recovery is highly variable and currently not predicable. It depends largely on the brain’s “plastic” capacity for developing new functional connections in language networks. Although there currently are no recognized biological markers for assessing plasticity, a form of transcranial magnetic stimulation (TMS) may serve this purpose and provide a biomarker for language recovery. Non-invasive TMS stimulates the brain when an electromagnetic coil is placed on the scalp and a magnet then creates a rapidly changing magnetic field in the brain. One form of TMS called theta burst stimulation (TBS) has been shown to induce targeted and reversible changes in brain function, including motor physiology and language processing. The effect of TBS on neural function has been linked to known biological mechanisms of plasticity. The investigators hypothesize that TBS can assess plasticity and be used to predict aphasia recovery following stroke.

They predict that TBS-induced changes in motor responses will be strongly associated with similar changes in language performance in both healthy people and those with aphasia.
In the first of a planned two-phase study, the investigators will determine whether TBS can be used to predict plasticity of language areas in healthy volunteers. The researchers will temporarily interrupt participants’ normal language function. Then, they will assess each individual’s responsiveness to TBS using a physiologic measure of motor function and see whether this measure also predicts each individual’s responsiveness on language tasks. They also will explore whether age and a genetic factor—both known to influence plasticity—also influence motor responses. If this phase demonstrates feasibility, they then will undertake the same process in a phase II study with post-stroke aphasia patients.

If feasible and successful, this research ultimately would expand understanding of plasticity in language systems, develop a marker of language plasticity, and lead to more effective matching of patients to specific types of language therapies to improve outcomes.


Aphasia patients' responses to brain stimulation may predict their extent of language recovery - Phase I

Aphasia is a common and often devastating consequence of stroke, affecting approximately 1 million patients in the US, including 80,000 new patients annually. The course of recovery from aphasia is highly variable, and it is now understood that functional recovery after brain injury depends largely on the adaptive plasticity of neural systems. Although it has been recognized that individual variability may account for differences in functional resilience after neurologic insult, no validated neurophysiologic indicators of neuroplasticity are currently being used clinically to predict cognitive recovery from aphasia or other cognitive deficits after brain injury. Evidence indicates that variability in response to the application of transcranial magnetic stimulation (TMS) may index differences in cortical plasticity, both within the motor system and in other domains. Theta burst stimulation (TBS) is an effective TMS method for inducing persistent changes in motor physiology, and converging genetic, pharmacologic, and animal study data indicate that perturbations in cortical activity after TBS and other forms of TMS are closely linked to known mechanisms of neuroplasticity, such as long-term potentiation (LTP) and long-term-depression (LTD). The purpose of this proposal is to explore TMS as a potential tool for assessing neuroplasticity in the language system and to assess the utility of this technology as a biomarker for functional recovery in patients with aphasia. The first aim of the proposed project will test the hypothesis that individual differences in cortical plasticity account for differences in the responsiveness of language systems to neuromodulation. We will compare TBS-induced changes in motor evoked potentials (TBS-MEPs) in normal subjects to transient changes in language performance induced by TBS, with the prediction that TBS-MEPs will correlate with TBS-induced language changes. We also predict that factors known to influence the capacity for cortical plasticity–age and the presence of a common BDNF val66met polymorphism—will influence TBS-MEPs and TBS-induced language changes similarly. The second aim of the project will test the hypothesis that the capacity for neuroplasticity is a critical determinant of compensatory change in language systems in aphasia recovery. We have previously shown that TMS can be used to facilitate language performance in patients with chronic aphasia. We will therefore compare TBS-MEPs with the transient effects of a session of therapeutic TMS on language performance in subjects with chronic aphasia. Owing to the central role of plasticity in both motor and language systems, we hypothesize that TBS-MEPs will predict differences in transient improvement in language measures in response to stimulation. Achievement of the aims of this project will greatly expand knowledge about the nature of plasticity in language systems. Importantly, development of a marker of language plasticity will also lay the foundation for improved prognostication of aphasia outcomes, more appropriate stratification of therapeutic language interventions, and the further development of treatments aimed at facilitating adaptive change in language systems.

Investigator Biographies

Roy Hamilton, M.D.

Dr. Hamilton is an Assistant Professor of Neurology and the Director of the Laboratory for Cognition and Neural Stimulation at the University of Pennsylvania. He pursued his undergraduate education at Harvard University, obtaining a BA in Psychology in 1995, and thereafter attended Harvard Medical School and Massachusetts Institute of Technology, where he obtained his MD and a Masters Degree in Health Sciences Technology in 2001. He completed residency training in Neurology at the University of Pennsylvania in 2005 and subsequently pursued a fellowship in Cognitive Neurology, also at the University of Pennsylvania. The central thrust of his research is to use noninvasive brain stimulation to explore the characteristics and limits of functional plasticity in the intact and injured adult human brain. His group uses a combination of behavioral measures and noninvasive brain stimulation techniques, including transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS), to elucidate structure-function relationships related to normal cognition and to promote therapeutic reorganization of neural representations of cognitive functions in individuals who have suffered from brain injury.